Antibodies play a vital role in our immune response. They can inactivate viruses and bacterial toxins, and are essential in recruiting the complement system and various types of white blood cells to kill invading microorganisms and large parasites. Antibodies are synthesized exclusively by B lymphocytes and are produced in millions of forms, each with a different amino acid sequence and a different binding site for an antigen.
A typical antibody is a Y-shaped molecule with two identical heavy (H) chains (each containing about 440 amino acids) and two identical light (L) chains (each containing about 220 amino acids). Proteolytic enzymes, such as papain and pepsin, can split an antibody molecule into different characteristic fragments. Papain produces two separate and identical Fab fragments, each with one antigen-binding site, and one Fc fragment. Pepsin produces one F(ab′)2 fragment. Alberts et al., Molecular Biology of the Cell, 2nd ed., 1989, Garland Publishing, Inc.
Both L and H chains have a variable sequence at their amino-terminal ends but a constant sequence at their carboxyl-terminal ends. The L chains have a constant region of about 110 amino acids long and a variable region of the same size. The H chains also have a variable region of about 110 amino acids long, but the constant region of the H chains is about 330 or 440 amino acid long, depending on the class of the H chain. Alberts et al., Molecular Biology of the Cell, 2nd ed., 1989, Garland Publishing, Inc.
The association between the four chains involves both covalent and noncovalent interactions. The covalent interactions are disulfide bonds formed between the cysteine residues in the carboxyl terminus of the light chain and the CH1 domain of the heavy chain and disulfide bonds formed between the cysteine residues in the hinge regions of the two heavy chains.
Natural immunoglobulins have been used in assays, diagnosis and, to a more limited extent, therapy. However, such uses, especially in therapy, have been hindered by the polyclonal nature of natural immunoglobulins. The advent of monoclonal antibodies of defined specificity increased the opportunities for therapeutic use. Therapeutic monoclonal antibodies usually contain some microheterogeneity resulting from post-translational modifications and degradation events that occur during the production process and throughout the shelf-life of the biopharmaceutical product. The present invention provides a novel modification of monoclonal antibodies.
Citation or discussion of a reference herein shall not be construed as an admission that such is prior art to the present invention.